Molecular Biology of the Gene, 5/E--- Watson et al. (2004) Part I: Chemistry and Genetics Part II: Maintenance of the Genome Part III: Expression of the Genome Part IV: Regulation Part V: Methods
Chemistry and Genetics Ch 1: The Mendelian View of the World Ch 2: Nucleic Acids convey genetic information Ch 3: The importance of weak chemical interactions Ch 4: The importance of high-energy bonds Ch 5: Weak and strong bonds determine macromolecular structure
Chapter 3: The importance of weak chemical interactions Weak bonds indeed are vital for life, partly because they can form and break under the physiological conditions present with cells. (Dynamics is important)
Pages 45-53 are important to read List the reasons making weak bond vital for life
Ch 5: Weak and strong bonds determine macromolecular structure • Higher-order structures are determined by intra- and intermolecular interactions • The specific conformation of a protein results from its pattern of hydrogen bonds • Most proteins are modular, containing two or three domains • Weak bonds correctly position proteins along DNA and RNA molecules • Allostery: Regulation of a protein’s function by changing its shape
Why Watson et al. want to tell us some stories about genetics and chemistry before we start the molecular biology?
Genetics [课堂] Inheritable traits (Mendel) Genetic material-DNA (Avery) Central Dogma [中心法则] (Watson and Crick) • Chemistry-mechanisms [自学] • Weak chemical bond interactions • Strong chemical bond energy transfer • 3.Weak and strong bonds determine macromolecule structure
The focus of Ch1 and Ch2 Recognizing scientists and science 认识科学家和科学
Recognizing the life of scientists (认识科学家的生活). • Recognizing the value and nature of science (认识科学的价值和本质). • Recognizing the noble characters displayed by scientists (认识科学家的可贵品格): love of the beauty of nature (对大自然美妙的热爱), the faith of your own creativity (对自己创造能力的信心) and the hope to be recognized (对科研成果被认可的盼望和执着-communication is important).
Chapter 1: The Mendelian View of the World (蒙德尔学派的人看世界) To explain how the genetic traits (遗传特性) are transferred from the parents to the offsprings.
Recognizing the life of a scientist: Box 1-1 Two important lessons to learn from Mendel’s discovery • The attitude to science:interested in discovering the wonders of the nature (laws, mechanisms) • The principle to conduct science:using simple models to understand the complicate or unknown story
Recognizing the beauty of science: Mendel’s discovery The principle of independent segregation（独立分离定律）(Mendel’s first law) ---The trait appearing in F1 progeny is called dominant; the one not appearing is called recessive. ---The various traits are controlled by pairs of factors (which we now call genes) Figure 1-1 How Mendel’s first law explains the 3:1 ratio of dominant to recessive phenotypes among the F2 progeny.
Recognizing the beauty of science: Mendel’s discovery Some alleles are neither dominant or recessive (And some phenotypes are determined by more than one gene) (The luck of Mendel’s discovery: a simple trait) Figure 1-2 The inheritance of flower color in the snapdragon (金鱼草).
Recognizing the beauty of science: Mendel’s discovery Principle of independent assortment（自由组合定律）(Mendel’s second law) ---When more than one characteristic are examined, the progenies showing recombined traits appear. Figure 1-3 How Mendel’s second operate.
Discussion 1 Why Mendelianism and Darwinism conflicted initially, how the conflict was resolved? (P15-16)
Discussion 2: Scientist and Science A hypothesis/theory that is too broad to be specify or to be tested in the strict concept of science: too complicate and can be revised forever if you do not want to give it up. A testable hypothesis/theory: Simple and beautiful
Chapter 2: Nucleic Acids convey genetic information The stories/efforts led to the fundamental knowledge of life, which open a new era of modern biology.
Ch 2 Nucleic Acids convey genetic information Avery’s Bombshell (1944): DNA can carry genetic specificity The Double Helix (1953) The genetic information within DNA is conveyed by the sequence of its four nucleotide building blocks The Central Dogma (1956) Establishing the direction of protein synthesis The Era of Genomics (2000)
Breakthrough in the thinking darkness The background of the discovery By the 1930s, geneticists began speculating as to what sort of molecules could have the kind of stability that the gene demanded, yet be capable of permanent, sudden change to the mutant forms that must provide the basis of evolution... It was generally assumed that genes would be composed of amino acids because, at that time, they appeared to be the only biomolecules with sufficient complexity to convey genetic information. This hypothesis is eventually dead from its shaking base and attractive complexity.
Avery’s Bombshell (1944): DNA can carry genetic specificity A story written for 16 years
1944 by Osward T. Avery The transforming activity was destroyed by deoxyribonuclease (available at the time), but not by ribonuclease nor various proteolytic enzymes
Thinking 1: what do you learn from the efforts of George W. Beadle and Edward Tatum (1940s), Frederick Griffith (1928),Osward T. Avery (1940s) Thinking 2: Why Avery made more recognizable contribution to the field than did Griffith?
The Double Helix (1953) The foundation of molecular biology Francis H. Crick James D. Watson
Crick is best known for his work in the discovery of the double helix, but since then he has made many other discoveries. After his discovery of the double helix, Crick went to work on finding the relationship between DNA and genetic coding. During this study with Vernon Ingram, they discovered the function of the genetic material in determining the specificity of proteins. In 1957, Crick began work with Sydney Brenner to determine how the sequence of DNA bases would specify the amino acid sequence in proteins. • Crick "established not only the basic genetic code, but predicted the mechanism for protein synthesis" (McMurray, 427) This worked led to many RNA/DNA discoveries and helped in the creation of the DNA/RNA dictionary. In 1960 Crick began to study the structure and possible functions of certain proteins associated with chromosomes called histones. Crick finally left Cambridge Laboratories in 1976 to become Kieckhefer Professor at Salk Institute for Biological Studies in San Diego, California. It was there that Crick began his present project of the study of the brain.
Rosalind Elsie Franklin: Pioneer Molecular Biologist From www.sdsc.edu/ScienceWomen/franklin.html (San Diego Supercomputer Center)
The Central Dogma (1953-1956) Setting the platform for molecular biology only takes 0.5 year or 3.5 years Exciting days of biologists Transcription RNA Protein DNA Translation Replication
The revised central dogma ---The framework of this course 基因组的保持 基因组的表达 RNA processing Gene regulation
Ch 2 Nucleic Acids convey genetic information The purpose of Molecular Biology of the genes is to provide a firm foundation for understanding how DNA functions as the template for biological complexity. Remember: this book is living in the age of the Central Dogma in understanding life, post-genomic era will certainly tell us a more complex but I hope a clear story of life.
Part 2, Maintenance of the Genome, describes the structure of the genetic material and its faithful duplication. Part 3, Expression of the Genome, shows how the genetic instructions contained in DNA is converted into proteins Part 4, Regulation, describes strategies for differential gene activity that are used to generate complexitywithin the organisms and diversity among organisms
Part 5, Methods, describes various laboratory techniques, bioinformatics approaches, and model systems that are commonly used to investigate biological problem.